AU609969B2 - Method of preparing lactulose - Google Patents

Method of preparing lactulose Download PDF

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Publication number
AU609969B2
AU609969B2 AU33391/89A AU3339189A AU609969B2 AU 609969 B2 AU609969 B2 AU 609969B2 AU 33391/89 A AU33391/89 A AU 33391/89A AU 3339189 A AU3339189 A AU 3339189A AU 609969 B2 AU609969 B2 AU 609969B2
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AU
Australia
Prior art keywords
isomerisation
lactose
lactulose
hydrogen peroxide
basic
Prior art date
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Expired
Application number
AU33391/89A
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AU3339189A (en
Inventor
Walterus T. De Haar
Hendrik Pluim
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Duphar International Research BV
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Duphar International Research BV
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Publication date
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Publication of AU3339189A publication Critical patent/AU3339189A/en
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H3/00Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms
    • C07H3/04Disaccharides

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Saccharide Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention relates to a new method of preparing lactulose by basic isomerisation of lactose. According to the invention the reaction mixture is treated with hydrogen peroxide or sodium chlorite to obtain lactulose of an acceptable colour for a pharmaceutical product. Preferably 0.5 - 5 g of hydrogen peroxide are used per kg of lactose. 1H2O.

Description

AUSTRALIA
Patents Act COMPLETE SPECIFICATICtN
(ORIGINAL)
Class Int. Class Application Number: Lodged: Complete Specification Lodged: Accepted: Published: Priority This document cnan h Related Art: Earnendrnts made tinder 0 00Section 49 and is correct for ~p 1rinting.
APPLICANT'S REFERE29E: DIR 0414A/M/JNK 'Name(s) of Applicant(s): Duphar International Research B.V Address(es) of Applicant(s): C.J. van I-outenlaan 36, Weesp, THE NETHERLANDS.
Address for Service is: I: PHILLIPS OR4CN>DE FITZPATRI1CK Patent and Trade Mark Attorneys 367 Collins Street Melbourne 3000 AUSTRALIA Complete Specification for the invention entitled: METHOD OF PRPAM11rG LACThLOSE Our Ref 128240 POF Code: 1596/463997 The following statement is a full description of this invention, including the best method of performing it known to applicant(s): 6003q/1 -1- PHILLIPS ORMONDE AND FITZPATRICK Patent and Trade Mark Attorneys 367 Collins Street Melbourne, Australia P17/1179 STUART TAYLOR la DIR 0414 Method of preparing lactulose The invention relates to a new method of preparing lactulose by basic isomerisation of lactose.
A conventional method of preparing lactulose from lactose comprises the basic isomerisation of lactose at elevated temperature. During the said isomerisation reaction are formed in addition to lactulose decomposition products thereof, and a brown-coloured reaction mixture is obtained.
It is known that the brown colouring of the mixture during the isomerisation can be mitigated by carrying out the isomerisation in the presence of sodium sulphite, sodium bisulphite or sodium phosphite. It is assumed that the sulphite ion, bisulphite ion or phosphite ion reacts with the decomposition products of lactulose while forming 4 t€ sugar sulphonic acids and sugar phosphonic acids which can then be removed by means of ion exchangers.
Such a method is known from Netherlands Patent Specification no. 165467 in which the use of sodium sa o sulphite, from United States Patent Specification no.
4,536,221 in which the use of sodium bisulphite, and from Netherlands Patent Application No. 7907259 in which the use 00oo 25 of sodium phosphite as an oxidant is described. However, the formed sugar sulphonic acids and sugar ph sphonic acids are hard to decompose on purifying the waste water in a t oO water treatment plant and hence they are ecologically S°,g unsound.
It has now been found that such problems do not i present themselves when hydrogen peroxide or sodium chlorite is used in the method mentioned in the preamble instead of sulphite, bisulphite or phosphite.
Hydrogen peroxide both in an acid medium and in a basic medium may serve as an oxidant and consequently can -iboxidize the decomposition products of lactulose which are formed during the isomerisation to (carboxylic) acids which can be removed by means of ion exchangers.
Excellent results are also obtained with sodium chlorite as a coreagent besides the sodium hydroxide required for the isomerisation, but as a result of the formation of corrosive compounds, for example, chlorine and chlorodioxide, during the reaction, higher requirements are imposed on the apparatus than when hydrogen peroxide is used.
Therefore according to the present invention there is provided a method of preparing lactulose by basic isomerisation of lactose, wherein the reaction mixture is treated with hydrogen peroxide or sodium chlorite.
According to a preferred embodiment of the method according to the invention hydrogen peroxide is used as an oxidant and is added after the basic isomerisation reaction of 0 0 0o lactose to lactulose. Preferably 0.5-5 g of hydrogen peroxide oo is used per kg of lactose.1H 0.
0 0 0 0 0 00 0o 00 0 0 0 0 0 0 0 00 00 0 0 0 0 o o 00 00 0 0 0 0 0 0 0 i 000000 0 0 0000ooo o 00 0 00 0 0 00 0 00o 0 00 0 0 0 0 0 00 0 o 000000 0 0 S MW/2320U
L-
DIR 0414 oxidize thed CO0 mpo Siti on products. of l-a tuose which- are formed during the iscmerisation to (carboxylic) acids whi can be removed by means of ion exchangers.
Excellent results are also obtained with s ium chlorite as a coreagent besides the sodiu ydroxide required for the isomerisation, but a result of the formation of corrosive compound for example, chlorine and chlorodioxide, during the action, higher requirements are imposed on the appara s than when hydrogen peroxide is used.
Accord cg to a preferred embodiment of the method accord' g to the invention hydrogen peroxide is used as an o 'dant and is added after the basic isomerisation reaction a 0o o 00 00 0 0 0 0 0 00 00 oo o0 a 0 0 00 o 0o 00 o 0 0 0 o00 on 0 00 0000 0 0000.
Q1L Q4QRQ 0 -QQU4---- 15 It is recommendable in particular to add hydrogen peroxide, for example, in the form of 17.5% solution, to the isomerisation mixture at a temperature of approximately 50°C, after the pH of the mixture has become smaller than 7. However, it is also possible to add hydrogen peroxide at 20 a higher temperature of approximately 95°C under basic conditions (pH 7.5-8.0).
The reaction mixture, after isomerisation and treatment with H 2 0 2 or NaC102, is processed in the conventional manner. The non-converted lactose is removed 25 by crystallisation and is used again. The mixture comprising lactulose and decomposition products is purified by means of ion exchangers.
By using H 2 0 2 or NaC102 instead of Na 2
SO
3 NaHSO 3 and Na 3 P0 3 used so far, the decomposition products of lactulose which are formed during the isomerisation pre converted into readily decompcsable sugar carboxylic acids which cause no problems ecologically.
Z
1 0 a 4 0 o a a a i j.i r 14 3 DIR 0414 EXAMPLE I The data and results of a number of experiments on a laboratory scale are recorded in table A hereinafter. In all the experiments the isomerisation of lactose to lactulose was carried out with NaOH, optionally in the presence of Na 2
SO
3 The addition of H 2 0 2 according to the invention after the isomerisation reaction was carried out in two different manners: method I: in basic conditions (pH 7.5-8) at approx. ,10 method II: in acid conditions (pH at approx. 000000 0 0 0000 0 0 00 a Table A 00 00 o O 00 00 o 0 0 0 0 00 00 00 0000 0 0 0 0 o 0 0o ao 000 0 0 000 15 20 Exp. NaOH Na 2
SO
3
H
2 0 2 Method Colour after No. g/kg lactose.lH20 (ditto) (ditto) isomerisation 1 2.5 13-16 2 2.0 2.0 3-10 3 2.5 2.4 I 2-3 4 2.5 2.4 II 6-7 The colour is compared with the Gardner scale, a colour scale from 1 (colourless) to 20 (reddish brown).
On the basis of the colourindex the use of H 2 0 2 25 according to method I were to be preferred. On the basis of results of stability experiments (ageing tests), however, it seems that method II leads to a slightly better result.
EXAMPLE II The data and results of a number of experiments on a laboratory scale are recorded in table B. As in example I in all the experiments the isomerisation was carried out 4 DIR 0414 with NaOH, optionally in the presence of Na 2
SO
3 The addition of NaC1O 2 was carried out simultaneously with the addition of NaOH at about Table B Exp. Na0H Na 2 S0 3 NaClO 2 Colour after No. g/kg lactose.1H 2 0 (ditto) (ditto) isomerisation* 5 2.5 -13-16 6 2.0 2.0 -3-10 7 1.9 2 .7 3-8 8 3.5 -1.2 13-16 9 3 .5 3 3.9 3-8 00 0 0 t 000 0 o 0 00 '0 00 00 00 00 00 00'015 0000 0 0 Gardner scale 0 000 0 00 00 0 C, 00 0000 0 0 Ij 0 a0

Claims (5)

1. A method of preparing lactulose by basic isomerisation of lactose, wherein the reaction mixture is treated with hydrogen peroxide or sodium chlorite.
2. A method as claimed in claim 1, wherein 0.5-5 g of H202 is used per kg of
3. A method as claimed in claim 1 or claim 2 wherein H202 is added at a pH lower than 7.0, and at a temperature of approximately 50 0 C.
4. A method as claimed in claim 1 or claim 2 wherein H202 is added in basic conditions at pH 7.5-8.0 and at a temperature of approximately 95 0 C. A method as claimed in claim 1, wherein about 1.2 to about 3.9 g of NaC10 2 are used per kg of lactose. 1H 2 0 at a temperature of about 95 0 C and in basic conditions.
6. A method as claimed in claim 1 substantially as hereinbefore described with reference to any one of the o o examples. 0 0 0 a o0 o 0 o o a0 o° DATED: 7 February 1991 0 0 0 o 0 00 0 a PHILLIPS ORMONDE FITZPATRICK 0 0 Patent Attorneys for: DUPHAR INTERNATIONAL RESEARCH B.V. S CC o to6 o G 0 t 0 4\DMW/2320U ^Liy
AU33391/89A 1988-04-28 1989-04-26 Method of preparing lactulose Expired AU609969B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NL8801102 1988-04-28
NL8801102 1988-04-28

Publications (2)

Publication Number Publication Date
AU3339189A AU3339189A (en) 1989-11-02
AU609969B2 true AU609969B2 (en) 1991-05-09

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AU33391/89A Expired AU609969B2 (en) 1988-04-28 1989-04-26 Method of preparing lactulose

Country Status (13)

Country Link
US (1) US5026430A (en)
EP (1) EP0339749B1 (en)
JP (1) JP2675614B2 (en)
AT (1) ATE113055T1 (en)
AU (1) AU609969B2 (en)
CA (1) CA1319933C (en)
DE (1) DE68918887T2 (en)
DK (1) DK170977B1 (en)
ES (1) ES2061936T3 (en)
IE (1) IE65054B1 (en)
IL (1) IL90086A0 (en)
NZ (1) NZ228900A (en)
ZA (1) ZA893097B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3920288B2 (en) * 2002-06-04 2007-05-30 森永乳業株式会社 Method for producing lactulose-containing powder composition, lactulose-containing powder composition obtained by the method, and feed additive
RU2734782C1 (en) * 2020-04-15 2020-10-23 Общество с ограниченной ответственностью «Завод глубокой переработки молока «ЛактоПром» Lactulose production method

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4555271A (en) * 1983-06-20 1985-11-26 Sirac Spa Process for purifying lactulose syrup
AU3145989A (en) * 1988-03-18 1989-09-21 Duphar International Research B.V. Method of preparing solid lactulose
AU4716689A (en) * 1988-12-21 1990-06-28 Duphar International Research B.V. Method of manufacturing lactulose

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AT288595B (en) * 1969-02-07 1971-03-10 Laevosan Gmbh & Co Kg Process for the production of lactulose concentrate
US4196017A (en) * 1979-01-29 1980-04-01 Holly Sugar Corporation Method for reducing color impurities in sugar-containing syrups
US4536221A (en) * 1982-12-17 1985-08-20 Sirac Spa Process for preparing lactulose from lactose, in the form of a syrup or a crystalline product

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4555271A (en) * 1983-06-20 1985-11-26 Sirac Spa Process for purifying lactulose syrup
AU3145989A (en) * 1988-03-18 1989-09-21 Duphar International Research B.V. Method of preparing solid lactulose
AU4716689A (en) * 1988-12-21 1990-06-28 Duphar International Research B.V. Method of manufacturing lactulose

Also Published As

Publication number Publication date
JPH01313490A (en) 1989-12-18
ATE113055T1 (en) 1994-11-15
IL90086A0 (en) 1989-12-15
DK198989D0 (en) 1989-04-25
DE68918887T2 (en) 1995-02-23
IE65054B1 (en) 1995-10-04
DK198989A (en) 1989-10-29
AU3339189A (en) 1989-11-02
CA1319933C (en) 1993-07-06
ES2061936T3 (en) 1994-12-16
ZA893097B (en) 1990-01-31
DK170977B1 (en) 1996-04-09
NZ228900A (en) 1990-12-21
EP0339749A1 (en) 1989-11-02
EP0339749B1 (en) 1994-10-19
JP2675614B2 (en) 1997-11-12
US5026430A (en) 1991-06-25
DE68918887D1 (en) 1994-11-24
IE891331L (en) 1989-10-28

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